Circulating extracellular vesicles carrying Firmicutes DNA reflect the local immune status and may predict clinical response to cancer immunotherapy in urothelial carcinoma

2022 Fiscal Year Final Research Report

• Project/Area Number: 21K20968
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0906:Surgery related to the biological and sensory functions and related fields
• Research Institution: Osaka University
• Principal Investigator: Yamamoto Akinaru 大阪大学, 医学部附属病院, 医員 (50909653)
• Project Period (FY): 2021-08-30 – 2023-03-31
• Keywords: 尿路上皮癌 / 血液診断薬 / 血液細菌叢 / エクソソーム / 腫瘍免疫 / 腫瘍微小環境

Outline of Final Research Achievements

The smaller amount of peripheral EVs carrying Firmicutes DNA was significantly correlated with the higher number of infiltrating T cells within tumor tissues (CD3; p=0.015, CD4; p=0.039, CD8; p=0.008) and the higher expression of activation markers on their surface (ICOS on both CD4; p=0.001 and CD8 T cells; p=0.016 and 4-1BB on CD4 T cells; p=0.016). All patients with higher Firmicutes abundance had disease progression (p=0.026) and significantly inferior prognosis for immunotherapy (p=0.035).Firmicutes abundance carried by EVs in the blood can reflect the local immune status and predict the efficacy and prognosis of UC immunotherapy.

Free Research Field

泌尿器科癌

Academic Significance and Societal Importance of the Research Achievements

これまでに尿路上皮癌の血液バイオマーカーは存在しておらず、尿を用いた尿細胞診検査や膀胱鏡検査を用いて尿路上皮癌の診断は行われてきた。しかし、その感度の低さや侵襲性の高さから、簡便な血液バイオマーカーの作成が希求されていた。そこで、我々の開発した血液内エクソソームの細菌遺伝情報を用いたバイオマーカーの創出は非常に新規性が高く、臨床応用されることができれば非侵襲的に尿路上皮癌患者の早期発見に結び付くと考える。また、近年癌治療の主流ともなりつつある免疫療法の治療効果も予測可能であり、治療適応患者の選出にも役立つ可能性が考えられる。